Study of ASTX295 in Patients With Solid Tumors With Wild-Type p53

Exclusion Criteria

• •Medical Conditions
• •1. Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
• •2. Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise subject safety, or the integrity of study outcomes, or interfere with the absorption or metabolism of ASTX295.
• •3. History of, or at risk for, cardiac disease, as evidenced by any of the following conditions:
• •1. Abnormal left ventricular ejection fraction.
• •2. Congestive cardiac failure of ≥Grade 3.
• •3. Unstable cardiac disease.
• •4. History or evidence at Screening of long QT interval corrected for heart rate (QTcF), ventricular arrhythmias, clinically significant bradyarrhythmias, third-degree atrioventricular (AV) block, presence of cardiac pacemaker or defibrillator, or other clinically significant arrhythmias.
• •5. Screening 12-lead electrocardiogram (ECG) with measurable QTcF interval of ≥470 msec. (Fridericia's formula should be used).
• •4. Known advanced human immunodeficiency virus (HIV) infection (including AIDS): clinical stage ≥ 3 according to WHO classification and/or HIV-associated immunodeficiency.
• •5. Known active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (Inactive Hepatitis Carrier and subjects with laboratory evidence of no active replication on antivirals - viral load below limit of detection- will be permitted).
• •6. Known brain metastases, unless previously treated and clinically stable for at least 4 weeks with or without steroids.
• •7. Known significant mental illness or other conditions, such as active alcohol or other substance abuse that, in the opinion of the investigator, predispose the subject to high risk of noncompliance with the protocol treatment or assessments.
• •Prior/Concomitant Therapy
• •8. Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX295), as follows:
• •1. Cytotoxic chemotherapy within 3 weeks prior. Any encountered treatment-related toxicities (excepting alopecia) must be stabilized or resolved to ≤Grade 1.
• •2. Monoclonal antibodies, biologics, or immunotherapy within 4 weeks prior. Any encountered treatment-related toxicities must be stabilized or resolved to ≤Grade 1.
• •3. Molecularly targeted drug or other investigational drugs, without the potential for delayed toxicity, within 4 weeks of the first dose of study treatment or 5 half-lives (minimum 14 days), whichever is shorter. Any encountered treatment-related toxicities must be stabilized or resolved to ≤Grade 1.
• •4. Major surgery or radiation within 4 weeks prior to first dose (palliative radiotherapy to a single lesion within 2 weeks).
• •9. Prior treatment with MDM2 antagonist
• •10. Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to ASTX295.
• •Participants are excluded from the Phase 2 part of the study if any of the following additional criteria apply:
• •11. Active malignancy other than the cancer under study (excludes low risk prostate cancer or early breast cancer with or without hormonal therapy, basal cell carcinoma of the skin and superficial bladder cancer).